Association of tumor growth on nude mice and poor clinical outcome in soft tissue sarcoma patients.

Abstract

Permanent growth in nude mice (PGNM) may be associated with poor clinical outcome. We tested this hypothesis in a group of soft tissue sarcoma (STS) patients. Small chunks from fresh tumor biopsies of 81 patients with STS were transplanted subcutaneously into NMRI-nu/nu nude mice. Tumor cell lines exhibiting growth in nude mice for more than three tumor passages were considered as permanently established. Clinical outcome of all patients was monitored with a median follow-up of 38 months. 39/81 (48%) STSs exhibited PGNM. High grade, high S-phase proportion, and aneuploidy were significant predictors of PGNM. Overall survival (OS) at 3 years was 21% (+7% standard error of median) for STS patients with PGNM and 53% (+/-8%) for patients without PGNM (P<0.01). Considering only patients without distant metastasis at the time of biopsy (n = 49), 3-year-OS was 25% (+/-10%) and 71% (+/-9%) for STS with PGNM and without PGNM, respectively (P<0.01). In the univariate analysis, PGNM, aneuploidy high S-phase proportion, tumor location at the trunk, high tumor grade, and non-liposarcoma histology were associated with reduced survival time. In the multivariate analysis, aneuploidy and tumor location at the trunk were the only independent predictors of overall survival. Permanent growth of STS on nude mice is associated with poor clinical outcome in the univariate analysis, but is not an independent predictor of survival in the multivariate analysis due to a strong co-correlation to other known adverse prognostic factors.